HUMAN PEX7 ENCODES THE PEROXISOMAL PTS2 RECEPTOR AND IS RESPONSIBLE FOR RHIZOMELIC CHONDRODYSPLASIA PUNCTATA

Rhizomelic chondrodysplasia punctata (RCDP) is a rare autosomal recess ive phenotype that comprises complementation group 11 of the peroxisom e biogenesis disorders (PBD). PEX7, a candidate gene for RCDP identifi ed in yeast, encodes the receptor for peroxisomal matrix proteins with the type-2 peroxisome targeting signal (PTS2). By homology probing we identified human and murine PEX7 genes and found that expression of e ither corrects the PTS2-import defect characteristic of RCDP cells. In a collection of 36 RCDP probands, we found two inactivating PEX7 muta tions: one, L292ter, was present in 26 of the probands, all with a sev ere phenotype; the second, A218V, was present in three probands, inclu ding two with a milder phenotype. A third mutation, G217R, whose funct ional significance is yet to be determined, was present in five proban ds, all compound heterozygotes with L292ter. We conclude that PEX7 is responsible for RCDP (PBD CG11) and suggest a founder effect may expla in the high frequency of L292ter.